Scabies Infestation
Scabies is a public health concern of global proportion, affecting an estimated 300 million people worldwide each year [Chosidow, O., Clinical practices. Scabies”; N. Engl. J. Med.; Vol. 354, pp. 1718-1727, 2006]. The disease dates back to the 1700's when the Sarcoptes scabiei mite was first identified as the culprit pathogen. As a highly contagious infectious disease of the skin, scabies is readily spread by direct physical contact. It affects people of all races and social classes and occurs in all age groups and both genders [Wendell, K. et al., “Scabies and pediculosis pubis: an update of treatment regimens and general review”; Clin. Infect. Dis.; Vol. 35; pp. S146-S151, 2002]. It is a common sexually transmitted disease; however, it is often transmitted nonsexually and is easily spread within families and among people living in crowded conditions [Wendell, K. et al., 2002]. Hospitals, nursing homes, and long-term care facilities are likely sites of scabies epidemics [Habif, T. P., “Scabies”; Clinical Dermatology, 4th ed., New York: Mosby; pp. 497-505, 2004; Wendell, K. et al., 2002]. Often referred to as the “itch mite,” scabies can cause intense, unbearable itching, clinically described as pruritis [McCarthy, J. S., et al., “Scabies: more than just an irritation”; Postgrad. Med. J.; Vol. 80, pp. 382-387, 2004; Orion, E., et al., “Ectoparasitic sexually transmitted diseases: scabies and pediculosis”; Clin Dermatol.; Vol. 22, No. 6, pp. 513-519, 2004]. Complications include bacterial superinfection, sepsis, glomerulonephritis and progression to Norwegian or crusted scabies—a more severe, life-threatening form of the disease [Walton, S. F., et al., “Scabies: new future for a neglected disease”, Adv Parasitol., Vol. 57, pp. 309-376, 2004; Chosidow, O., Scabies and pediculosis; Lancet, Vol. 355, pp. 819-26, 2000; Habif, T. P., 2004; Wendell, K. et al., 2002; McCarthy, J. S., et al., 2004].
Today, scabies is increasingly found among immunocompromised patients (i.e., those with HIV infection, cancer, diabetes, organ transplant and those receiving immunosuppressive therapies), where mite burdens can rise to thousands or millions and infestation becomes much more diffuse and widespread over the body. This not only increases the risk of secondary bacterial infection, a potentially serious outcome, but also increases the likelihood of transmission to noninfected individuals [Mathisen G., “Of mites and men: lessons in scabies for the infectious diseases clinician” (Editorial response); Clin. Infect. Dis., Vol. 27, pp. 646-647, 1998].
The scabies mite (i.e., Sarcoptes scabiei) is a small, rounded, 8-legged parasitic insect that is too small to be seen by the naked eye without magnification. Attracted to warmth and odor, the female mite burrows into the skin, lays eggs, and produces toxins that cause a hypersensitivity reaction and the cardinal symptom of pruritis. Larvae, or newly hatched mites, travel to the skin surface, lying in shallow pockets where they mature into adult mites. Within 2 months, an infected individual may have 25 adult female mites living in the superficial layers of their skin. Within 3 to 4 months, as many as 500 mites may be present [Orion, E., et al., 2004]. Symptoms may not be initially noticeable, especially among patients with good hygiene and those who bathe regularly. Within several weeks, however, pruritis often becomes unbearable, keeping sufferers awake all night.
Scabies is almost always transmitted by close personal contact; only rarely is it contracted by way of contaminated clothing, towels or bedding [Johnston, G., et al., “Scabies: diagnosis and treatment”; BMJ; Vol. 331, pp. 619-622, 2005; U.S. Centers for Disease Control and Prevention (CDC). Parasitic Disease Information: Head Lice Fact Sheet. 2005]. Although scabies is not a condition exclusive to low-income families, it is more often associated with crowded living environments and poor hygienic conditions.
The most common site of scabies infestation in older children and adults, include the genitals, buttocks, fingers, wrists, elbows, armpits, knees and ankles [Habif, T. P., 2004]. Younger children and infants show more widespread involvement, including the palms and soles of the feet [Paller, A. S., et al., “Insect bites and parasitic infestations”; Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence; London: Elsevier, Ch. 18, p. 479, 2006]. However, scratching can spread scabies to non-infected areas of the body [Habif, T. P., 2004].
Diagnosis and Treatment
Diagnosis of scabies is generally made clinically by observing the skin burrows created by scabies mites, having the appearance of an excoriated papular rash [Flinders, D. C., et al., “Pediculosis and scabies”; Am. Family Physician, 2004]. Nodules, vesicles, pustles and eczema may also be present but are less specific signs of the disease. Lesions are most often symmetrical in distribution, affecting both the left and right sides of the body [Johnston, G., et al. 2005; Orion E, et al. 2004] Scraping of the burrows and subsequent examination under a microscope for mites, their eggs or fecal matter (“scybala”) leads to a definitive diagnosis [Rosen, T., et al., “Cutaneous manifestations of sexually transmitted diseases: scabies”; Med. Clin. North Am.; Vol. 82, pp. 1098-1099, 1998]. However, this technique may not always be revealing and is challenging to perform, even for highly-trained healthcare professionals [Karthikeyan, K., “Treatment of scabies: newer perspectives”; Postgrad. Med. J.; Vol 81, pp. 7-11, 2005]. As such, a definitive diagnosis is not always possible and clinicians must often rely exclusively on the physical examination and patient history.
A number of agents have been used for the management of scabies infestation, with varying rates of efficacy and varying labeled restrictions. Topical therapy is considered the mainstay of treatment, although oral medications are sometimes employed. In the U.S., relatively few agents are FDA approved for this indication. Commonly used treatments include topical permethrin 5% cream*, topical lindane (gamma benzene hexachloride) 1% lotion*, topical benzyl benzoate 10% and 25% lotion or emulsion, topical crotamiton 10% cream*, topical precipitated sulphur 3%-6% lotion or 5%, 10% or 40% in petrolatum, topical allethrin 0.6% aerosol, and oral ivermectin (*FDA-approved indication) [Chosidow 0.2006]. The current treatment for scabies using 1% lindane lotion or cream involves application and then rinsing off after eight hours [Chosidow O. 2006].
Lindane and permethrin are the best studied topical therapies, with comparable rates of efficacy noted in the largest comparative trial to date [Chosidow O. 2006; Schultz, M. W., et al., “Comparative study of 5% permethrin cream and 1% lindane lotion for the treatment of scabies”; Arch Dermatol.; Vol. 126, pp. 167-170, 1990]. Permethrin is approved as a first-line treatment. Lindane is indicated second line because of a relatively greater potential for neurologic side effects, although the vast majority of serious events have almost always resulted from product misuse [U.S. Food and Drug Administration (FDA). Lindane Post Marketing Safety Review. 2003]. Crotamiton is also FDA approved as a first-line intervention but is less effective and not often used. In select patients and settings, oral ivermectin has been shown to be efficacious; however, in the U.S., this is an off-label use [Chosidow O. 2006].
In many parts of the world, including the U.S., drug-resistant forms of scabies have been documented, further complicating disease management and containment of scabies outbreaks. Drug resistance has been reported for all of the commonly used agents, including permethrin, crotamiton, ivermectin and lindane. [Johnston G, et al. 2005; McCarthy J S, et al. 2004] The unpredictable nature of resistance and geographical variability necessitates the need for a variety of approved treatment options.
Lindane (gamma-HCH or BHC)
Lindane is an insecticide, also known as gamma-hexachlorocyclohexane (HCH) and benzene hexachloride (BHC). Its empirical formula is C6H6Cl6 and it has the following structural formula:

Lindane exerts its pharmacologic effects via absorption through the chitinous exoskeleton of arthropods (e.g, scabies mite) and subsequent stimulation of the central nervous system (CNS), resulting in convulsion and death.
Lindane Lotion, USP, 1% (“lindane lotion”) is approved by the FDA and strictly regulated as a prescription medication for the “second-line” treatment of scabies, meaning it is only indicated after first-line medicines have failed or cannot be tolerated. Lindane lotion has been used successfully in clinical practice for more than 50 years and has proven safe and effective when used as directed. However, systemic drug exposure and the potential risk for neurologic side effects have been raised as a concern. Young children, elderly and individuals of slight stature (weighing less than 50 kg) may be more susceptible to these adverse effects, and cautious use is recommended in these patient types [FDA Public Health Advisory, 2003]. Increased systemic exposure resulting from a higher surface-to-volume ratio has been proposed as a potential underlying factor.
Central nervous system stimulation, with symptoms ranging from dizziness to seizures, has been reported in association with the use of lindane lotion. However, the vast majority of medically significant neurologic events have almost always resulted from accidental oral ingestion or misuse of the product. Indeed, the FDA has quantified serious neurologic side effects associated with the proper use of lindane lotion as rare. [U.S. FDA Postmarketing Safety Review, 2003]. The most common side effects of topical lindane are non-serious reactions of the skin, such as dryness, itching and rash. Nonetheless, lindane medications were relegated to second-line treatment status in 1995 because of concerns relating to product misuse and associated risks. [U.S. Food and Drug Administration (FDA) Public health advisory: Safety of topical lindane products for the treatment of scabies and lice. Mar. 28, 2003]. Lindane medications were also limited to small, single-use 2 oz. bottles (compared with the original 16 oz. multi-dose bottles) in 2003 to further mitigate the risk of improper drug use.
Currently approved guidelines for lindane lotion instruct patients and caregivers to apply a thin film of medicine to the entire body from the neck down and then wash off after 8-12 hours. However, data show that peak blood levels of Lindane are achieved within 4-6 hours following topical application of 1% lindane in a lotion vehicle. [Ginsburg, et al., “Absorption of Lindane in infants and children”; J. of Pediatrics; Vol. 91, pp. 998-1000, 1977]. Moreover, inflammatory skin conditions, such as scabies, alter the epidermal barrier, making skin more permeable to topical therapies. [Ginsburg et al., 1977]
The literature reveals few studies of 1% lindane applied for less than 8 hours. For example, an unpublished report by Taplin et al. apparently alleges that there was little difference in the cure rate with application of a 1% lindane lotion for 6 hours, as compared with 24 hours [Shacter, B.; “Treatment of scabies and pediculosis with lindane preparation. An evaluation”, J. Am. Acad. Dermatol., Vol. 5, pp. 517-527, 1981]. Similarly, a branded 1% lindane solution marketed in France under the tradename Scabecid®, requires only a single 6-12 hour skin application [Buffet, M. et al., “Current treatment for scabies,” Fundamental & Clinical Pharmacology, Vol. 17 (2003), pp. 217-225].
There are also published reports of the use of lindane at concentrations less than 1% for the treatment of ectoparasitic disease. Specifically, the use of a 0.5% lindane lotion as a topical treatment for head lice has been described; however, the researchers concluded that the formulation was not sufficiently effective against head lice to justify its use for this particular indication. [Stichele, H. et al., “Systematic review of clinical efficacy of head lice,” British Medical Journal (1995), Vol. 311, pp. 604-608].
In light of these limited and somewhat conflicting reports, there remains a need to further explore methods of enhancing the risk-benefit balance of lindane lotion for the treatment of scabies infestation.